PB2089: IN-CLASS TRANSITION FROM PARENTERAL BORTEZOMIB TO ORAL IXAZOMIB IN NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM) ACCORDING TO AGE AND FRAILTY STATUS: UPDATED SUBGROUP ANALYSIS OF US MM-6
Authors: Saulius K. Girnius, Joshua Richter, Roger M. Lyons, Kimberly Bogard, Sudhir Manda, Ruemu E. Birhiray, Habte A. Yimer, Kim Tran, Suman Kambhampati, Jyoti Arora, Stephen Noga, Robert Rifkin
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Prolonged therapy with parenteral proteasome inhibitors (PIs) can improve outcomes in multiple myeloma (MM) but can be challenging to achieve in routine practice due to both treatment-related toxicity and administration burden, particularly for older and/or frail patients (pts), and those with comorbidities. For these pts, who are often not candidates for upfront stem cell transplantation, it is critical to determine ways to improve their depth and duration of response to treatment and to extend their progression-free survival (PFS). US MM-6 is a prospective, community-based phase 4 study of in-class transition (iCT) from parenteral bortezomib (V)-based induction to all-oral ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) in pts with NDMM (NCT03173092). Aims: US MM-6 aims to extend the duration of PI-based therapy and improve outcomes by maintaining a tolerable regimen that improves the depth and duration of response while maintaining pt quality of life (QoL). Results for the fully accrued dataset of 141 pts have been reported (Yimer, IMS 2022). Here, we report a subgroup analysis of clinical outcomes from US MM-6 by age and frailty status. Methods: Transplant-ineligible/delayed-transplant (≥24 months) NDMM patients with ≥stable disease after 3 cycles of V-based induction were enrolled at US community sites to receive ixazomib-Rd for up to 39 cycles or until progression/toxicity (Manda, CLML 2020). The primary endpoint was 2-year PFS. For this analysis, efficacy and safety endpoints were analyzed in pt subgroups defined by age (<75 vs ≥75 years [yrs]) and frailty status (non-frail vs frail) at enrollment. Frailty status was determined by utilizing a modified Charlson Comorbidity Index score, age, and ECOG performance status. Results: Among the 140 pts who received ixazomib-Rd (as of Oct 2022 [data cutoff]; 1 successfully screened pt was not treated), 59 (42%) were aged ≥75 yrs and 86 (61%) were classified as frail (Table). Overall median follow-up was 26.8 months; 12 vs 7% of pts aged <75 vs ≥75 yrs and 13 vs 8% of non-frail vs frail pts were ongoing on study treatment. The table presents median duration of ixazomib-Rd and of total PI-based therapy for the age and frailty subgroups. Across all subgroups, both ORR and CR rates increased from the end of V-based induction following iCT to ixazomib-Rd (Table). The 2-yr PFS rate was 72 vs 67% in pts aged <75 vs ≥75 yrs and 74 vs 68% in non-frail vs frail pts; these differences were not statistically significant. Median PFS and overall survival were not reached in any subgroup. Safety outcomes were generally comparable between the two age subgroups (Table), although certain grade ≥3 TEAEs were slightly more prevalent in older pts (including pneumonia; ≥5% difference). Incidences of grade ≥3 TEAEs (including pneumonia; ≥5% difference), serious TEAEs (including cellulitis; ≥5% difference), and TEAEs leading to dose modification (including thrombocytopenia and decreased neutrophil count; ≥5% difference) were lower in non-frail vs frail pts (Table). The number of on-study deaths was also slightly lower in non-frail vs frail pts (Table). Summary/Conclusion: In non-transplant NDMM pts, iCT from V-based induction to all-oral ixazomib-Rd permits long-term PI-based treatment and improves the depth of response while maintaining a tolerable safety profile. The expected decrement in outcomes associated with older age/frailty was not observed. Long-term triplet consolidation with ixazomib-Rd may provide an alternative approach to induction/maintenance in the community for pts with comorbidities and/or frailty who are not eligible for upfront transplantation.Keywords: Proteasome inhibitor, Real world data, Multiple myeloma, Age